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Identifying and Treating Patients with Insulin Resistance. Diagnosis of diabetes, IFG, and IGT. Plasma glucose (mg/dL). Fasting. 2-hr postload*. Casual. ≥200 – 140 to 199 (ADA) >140 to <200 (AACE). ≥126 100 to 125 (ADA) >110 to ≤126 (AACE) –. Diabetes

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diagnosis of diabetes ifg and igt
Diagnosis of diabetes, IFG, and IGT

Plasma glucose (mg/dL)

Fasting

2-hr postload*

Casual

≥200

140 to 199 (ADA)

>140 to <200 (AACE)

≥126

100 to 125 (ADA)

>110 to ≤126 (AACE)

Diabetes

Impaired fasting glucose (IFG)

Impaired glucose tolerance (IGT)

≥200

*Following equivalent of 75 g anhydrous glucose in water

ADA. Diabetes Care. 2005;28(suppl 1):S4-36.AACE. Endocr Pract. 2003;9:240-52.

metabolic syndrome diagnosis atp iii emphasizes clinical practice
Metabolic syndrome diagnosis: ATP III emphasizes clinical practice
  • Risk factor Defining level
  • Abdominal obesity (in) Waist: Men >40 Women >35
  • Triglycerides (mg/dL) ≥150
  • HDL-C (mg/dL) Men <40 Women <50
  • BP (mm Hg) ≥130/≥85
  • Fasting glucose (mg/dL) ≥110 (ADA ≥100)

NCEP ATP III. JAMA. 2001;285:2486-97.

metabolic syndrome diagnosis idf emphasizes central obesity
Metabolic syndrome diagnosis: IDF emphasizes central obesity

Plasma triglycerides >150 mg/dL*

HDL-C <40 mg/dL*

BP 140/90 mm Hg*

Fasting glucose 100 mg/dL or previously diagnosed type 2 diabetes

International Diabetes Federation

Central obesity

  • Plus any 2 of the following:
  • Defined according to waist circumference (ethnic- and gender-specific)

www.idf.org. Accessed August 2005.

*Or receiving specific treatment for this abnormality

idf ethnic and gender specific criteria for central obesity
IDF ethnic- and gender-specific criteria for central obesity

European37 32

Sub-Saharan African

Middle Eastern

South Asian35 32

South/Central American

Chinese35 32

Japanese34 35

Waist circumference (inches)

Men

Women

www.idf.org. Accessed August 2005.

metabolic syndrome diagnosis who emphasizes central role of insulin resistance
Metabolic syndrome diagnosis: WHO emphasizes central role of insulin resistance

Insulin resistance

  • Type 2 diabetes, or
  • Impaired fasting glucose, or
  • If fasting glucose <110 mg/dL, glucose uptake below lowest quartile

Plus any 2 of the following:

  • Antihypertensive medication and/or BP ≥140/90 mm Hg
  • Plasma triglycerides ≥150 mg/dL
  • HDL-C <35 mg/dL (men) or <39 mg/dL (women)
  • BMI >30 kg/m2 and/or waist-hip ratio >0.9 (men); >0.85 (women)
  • Urinary albumin excretion rate ≥20 µg/min or albumin-creatinine ratio ≥30 mg/g

Grundy SM et al. Circulation. 2004;109:433-8.Adapted from Alberti KG, Zimmet PZ. Diabet Med.1998;15:539-53.

other markers of insulin resistance
Other markers of insulin resistance
  • Family history of type 2 diabetes or CAD
  • Overactive sympathetic nervous system
  • Uric acid

Cohn GS et al. Am J Hypertens. 2005;18:1099-103.

abcs of coronary prevention
ABCs of coronary prevention

Adapted from Cohen JD. Lancet. 2001;357:972-3.

multidisciplinary consensus on managing metabolic syndrome
Multidisciplinary consensus on managingmetabolic syndrome

AHA / NHLBI / ADA

  • Modify lifestyle (weight loss, physical activity)
  • Assess risk
    • Framingham Risk Score
    • CRP (optional)
  • Reduce risk factors (ATP III, JNC 7, ADA)
    • Lipids, BP, thrombosis, glucose

“There is growing interest in the possibility that drugs that reduceinsulin resistance will delay onset of type 2 diabetes and will reduceCVD risk when the metabolic syndrome is present.”

Grundy SM et al. Circulation. 2004;109:551-6.

slide10

DPP: Impact of lifestyle intervention or metformin on diabetes

40

Placebo

N = 3234, no diabetes

Age 50

207 lbs

Glucose 107

P

30

Metformin

< 0.001

31%

Cumulative

incidence of

diabetes

(%)

20

Lifestyle

58%

< 0.001

  • Lose 5–10 lbs
  • Exercise 2.5 hrs/wk

10

0

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Year

DPP = Diabetes Prevention Program

DPP Research Group. N Engl J Med. 2002;346:393-403.

ukpds comparison of tight control of bp vs glycemia on risk of diabetes complications
UKPDS: Comparison of tight control of BP vs glycemia on risk of diabetes complications

Any diabetes-related

outcome

Diabetes-related

death

Coronaryheart

failure

Micro-vascular

Retinopathy

Stroke

0

–10

–20

%Patients

–30

–40

–50

–60

Tight BP (144/82 vs 154/87 mm Hg)

Tight glucose (A1C 7% vs 7.9%)

UKPDS = UK Prospective Diabetes Study

UKPDS Group. BMJ. 1998;317:703-13.

hps and cards benefits of lowering ldl c in diabetes
HPS and CARDS: Benefits of lowering LDL-C in diabetes

Event rate (%)

Δ LDL-C(mg/dL)*

Statin

better

Placebo

better

Statin

Placebo

P

HPS

0.73

34.8

9.4

9.3

5.8

12.6

13.5

9.0

<0.0001

0.0003

0.001

All diabetes

0.67

34.8

Diabetes, no CVD

0.63

46.4

CARDS

0.5

0.7

0.9

1

1.7

Relative risk

*Statin vs placebo

HPS = Heart Protection Study

CARDS = Collaborative Atorvastatin Diabetes Study

HPS Collaborative Group. Lancet. 2003;361:2005-16.Colhoun HM et al. Lancet. 2004;364:685-96.

slide13

ASCOT-LLA: Atorvastatin reduces CV events in patients with diabetes and hypertension

N = 2532, baseline LDL-C 128 mg/dL

14.0

Placebo

12.0

23% Risk reduction

P = 0.036

10.0

8.0

%

6.0

Atorvastatin 10 mg

4.0

2.0

HR = 0.77 (0.61–0.98)

0.0

Years

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Number at risk

1258

1231

1209

1191

1171

1065

699

370

Placebo

1274

1237

1219

1200

1175

1058

714

375

Atorvastatin

Nonfatal MI, CV mortality, UA, stable angina, arrhythmias, stroke, TIA, PAD, retinal vascular thrombosis, revascularization ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm

Sever PS et al. Diabetes Care. 2005;28:1151-7.

micro hope persuade reduction in primary outcome with acei
MICRO-HOPE, PERSUADE: Reduction in primary outcome with ACEI

25

25% Risk reduction

RR 0.75 (0.64–0.88)

P = 0.0004

Placebo

20

15

%

Ramipril

10 mg

10

5

0

0

1

2

3

4

5

Follow-up (years)

MICRO-HOPE

(N = 3577)

CV death/MI/stroke

PERSUADE

(N = 1502)

CV death/MI/cardiac arrest

25

Placebo

20

19% Risk reduction

P = 0.131

15

Perindopril

8 mg

10

5

0

0

1

2

3

4

5

Follow-up (years)

HOPE Study Investigators. Lancet. 2000;355:253-9.

Daly CA et al. Eur Heart J. 2005;26:1369-78.

steno 2 supports aggressive multifactorial intervention in type 2 diabetes
Steno-2 supports aggressive multifactorial intervention in type 2 diabetes

Objective: Target-driven, long-term, intensified intervention aimed at multiple risk factors compared with conventional therapy

Design: N = 160 patients with type 2 diabetes and microalbuminuria

Intensive treatment targets: BP <130/80 mm Hg

A1C<6.5%

Total-C <175 mg/dL

Triglycerides <150 mg/dL

Gæde P et al. N Engl J Med. 2003;348:383-93.

steno 2 effects of multifactorial intervention on cv outcomes
Steno-2: Effects of multifactorial intervention on CV outcomes

53% risk reductionP = 0.01

N = 160 with type 2 diabetes and microalbuminuria

60

50

Conventional

Primary composite outcome* (%)

40

30

20

Intensive

10

0

0

12

24

36

48

60

72

84

96

Follow-up (months)

Gæde P et al. N Engl J Med. 2003;348:383-93.

*CV death, MI, stroke, revascularization, amputation

summary
Summary
  • The majority of patients seen in cardiology practices have insulin resistance
  • Synergistic interaction of risk factors associated with insulin resistance places patients at high risk for CV disease
  • Current guidelines recommend aggressive multi-factorial treatment in patients with diabetes or prediabetes
  • PPAR modulation is a potentially important strategy for improving insulin sensitivity and blunting atherosclerosis progression